UV-associated decline in systemic folate: implications for human nutrigenetics, health, and evolutionary processes

Am J Hum Biol. 2017 Mar;29(2). doi: 10.1002/ajhb.22929. Epub 2016 Oct 22.

Abstract

Objectives: The purpose of this study was to examine whether UV exposure alters folate status according to C677T-MTHFR genotype, and to consider the relevance of this to human health and the evolutionary model of skin pigmentation.

Methods: Total Ozone Mapping Spectrometer (TOMS) satellite data were used to examine surface UV-irradiance, as a marker of UV exposure, in a large (n = 649) Australian cross-sectional study population. PCR/RFLP analysis was used to genotype C677T-MTHFR.

Results: Overall, cumulative UV-irradiance (42 and 120 days pre-clinic) was significantly negatively related to red cell folate (RCF) levels. When the cohort was stratified by MTHFR-C677T genotype, the relationship between UV-irradiance (42 days pre-clinic) and RCF remained significant only in the cohorts containing carriers of the T allele. Statistically significant z-score statistics and interaction terms from genotype and UV-irradiance (p-interaction) demonstrated that genotype did modify the effect of UV-irradiance on RCF, with the largest effect of UV being demonstrated in the 677TT-MTHFR subjects.

Conclusions: Data provide strong evidence that surface UV-irradiance reduces long-term systemic folate levels, and that this is influenced by the C677T-MTHFR gene variant. We speculate this effect may be due to 677TT-MTHFR individuals containing more 5,10CH2 -H4 PteGlu, and that this folate form may be particularly UV labile. Since UV-irradiance lowers RCF in an MTHFR genotype-specific way, there are likely implications for human health and the evolution of skin pigmentation.

Keywords: MTHFR; UV; evolution; folate; nutrigenetics; pigmentation.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cross-Sectional Studies
  • Female
  • Folic Acid / metabolism*
  • Folic Acid / radiation effects
  • Genotype
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Methylenetetrahydrofolate Reductase (NADPH2) / metabolism
  • New South Wales
  • Nutrigenomics
  • Ultraviolet Rays / adverse effects*

Substances

  • Folic Acid
  • Methylenetetrahydrofolate Reductase (NADPH2)